{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:18:38Z","timestamp":1765484318995,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypohidrotic ectodermal dysplasia is a rare condition characterized by hypohidrosis, hypodontia, and hypotrichosis. The disease can show X\u2010linked recessive, autosomal dominant or autosomal recessive inheritance trait. Of these, the autosomal forms are caused by mutations in either <jats:italic>EDAR<\/jats:italic> or <jats:italic>EDARADD<\/jats:italic>. To date, the underlying pathomechanisms or genotype\u2013phenotype correlations for autosomal forms have not completely been disclosed. In this study, we performed a series of in vitro studies for four missense mutations in the death domain of EDAR protein: p.R358Q, p.G382S, p.I388T, and p.T403M. The results revealed that p.R358Q\u2010 and p.T403M\u2010mutant EDAR showed different expression patterns from wild\u2010type EDAR in both western blots and immunostainings. NF\u2010\u03baB reporter assays demonstrated that all the mutant EDAR showed reduced activation of NF\u2010\u03baB, but the reduction by p.G382S\u2010 and p.I388T\u2010mutant EDAR was moderate. Co\u2010immunoprecipitation assays showed that p.R358Q\u2010 and p.T403M\u2010mutant EDAR did not bind with EDARADD at all, whereas p.G382S\u2010 and p.I388T\u2010mutant EDAR maintained the affinity to some extent. Furthermore, we demonstrated that all the mutant EDAR proteins analyzed aberrantly bound with TRAF6. Sum of the data suggest that the degree of loss\u2010of\u2010function is different among the mutant EDAR proteins, which may be associated with the severity of the disease.<\/jats:p>","DOI":"10.1111\/1346-8138.16610","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T03:34:36Z","timestamp":1666150476000},"page":"349-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Different degree of loss\u2010of\u2010function among four missense mutations in the <scp><i>EDAR<\/i><\/scp> gene responsible for autosomal recessive hypohidrotic ectodermal dysplasia may be associated with the phenotypic severity"],"prefix":"10.1111","volume":"50","author":[{"given":"Sasagu","family":"Yagi","sequence":"first","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine  Ube Japan"},{"name":"Department of Plastic Surgery Yamaguchi University Hospital  Ube Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichiro","family":"Yasuno","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine  Ube Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9944-2228","authenticated-orcid":false,"given":"Osamu","family":"Ansai","sequence":"additional","affiliation":[{"name":"Division of Dermatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-531X","authenticated-orcid":false,"given":"Ryota","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Dermatology Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-8073","authenticated-orcid":false,"given":"Yutaka","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yamaguchi University Graduate School of Medicine  Ube Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-021610-131501"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-409"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/11937"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/414913a"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.11.1661"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.9.1589"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13069"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/11943"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5491.523"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2013.08.006"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi405"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32855"},{"key":"e_1_2_7_14_1","first-page":"123","article-title":"Novel human pathological mutations. 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